CHAPTER 13
Valvular Heart Disease
Kenneth Ong, MD
Valvular heart disease affects 2.5% of the population in the United States with an equal gender distribution, but is found more frequently with increasing age (Go et al., 2013; Nkomo et al., 2006). It is expected that the prevalence will increase because of the disproportionate rise of the aging population and the widespread use of echocardiography to identify valvular heart disease even before the onset of clinical signs and symptoms. The primary care provider will therefore encounter such patients on a more frequent basis.
Healthy cardiac valves allow blood to flow forward without impedance while preventing significant retrograde movement. When the valves become diseased, their resulting pathophysiology may be characterized as predominantly stenotic, regurgitant, or a combination of both, with a severity that ranges from mild to severe. Initially, the heart has the capacity to compensate for these disturbances while maintaining forward cardiac output at a normal left ventricular filling pressure. As the valvular dysfunction progresses, the hemodynamic strain imposed on the heart may overcome such compensatory mechanisms and lead to clinical sequelae such as heart failure, myocardial ischemia, cardiac arrhythmias, and ultimately death.
In the management of each case of valvular heart disease, the provider must consider the following questions:
1. Is overall cardiac function adversely affected?
2. Are symptoms, if present, related to the valve dysfunction?
3. Is the valvular disease severe enough to warrant mechanical intervention?
The answers to these questions require an understanding of the anatomy and pathophysiology of valvular heart disease as well as recognition of the clinical features associated with each condition. This chapter reviews these issues for five major acquired left-sided valvular lesions: mitral stenosis, mitral regurgitation, mitral valve prolapse (MVP), aortic stenosis, and aortic regurgitation.
ANATOMY, PHYSIOLOGY, AND PATHOLOGY
Cardiac valves are thin, highly flexible structures that attach to a “ring” of fibrous tissue, which in turn is anchored to the walls of the heart. When fully opened, blood passes through without hindrance. Similarly, there is no significant blood flow across the valves when they are in the closed position. As the valves start to malfunction, their hemodynamic consequence depends on the involved valve and its main pathological process. In general, stenotic valves impose a pressure load to the chamber proximal to the stenosis, whereas regurgitant valves cause a volume overload state that affects chambers proximal and distal to it.
The specific compensatory mechanism therefore depends on the type of hemodynamic strain imposed on the heart by the dysfunctional valve. If the valve is stenotic, the reduced valve area obstructs forward blood flow. To maintain an adequate cardiac output, more pressure must be generated to propel blood across the valve. The primary pathophysiological mechanism to increase pressure within the cardiac chamber is the development of hypertrophy. While this is commonly seen in aortic stenosis as left ventricular hypertrophy, it does not develop in the relatively thin walls of the left atrium in the setting of mitral stenosis.
In contrast, if the valve is incompetent, net forward stroke volume is reduced in proportion to the degree of regurgitation. Therefore, to maintain adequate systemic cardiac output, chamber enlargement and increased ejection fraction must develop. The left atrium and left ventricle dilate to accommodate the increasing volume in mitral and aortic regurgitation, respectively. Whether hypertrophied or dilated, clinical decompensation occurs when the pressure or volume load overwhelms the ability of the heart to provide effective forward blood flow at a normal left ventricular end-diastolic pressure.
Mitral Stenosis
Mitral stenosis obstructs blood flowing from the left atrium into the left ventricle. As the impedance to flow increases, left atrial pressure must also increase in order to propel blood through the narrowed mitral orifice. As stated earlier, the left atrium has limited capacity to generate this pressure. As a result, this strain on the left atrium is subsequently transmitted backward toward the pulmonary circulation. Over time, pulmonary venous and arterial pressures increase, resulting clinically as exertional dyspnea. Because left ventricular filling occurs during diastole, any reduction in diastolic filling time, such as during tachycardia, may result in symptoms related to poor cardiac output, such as fatigue. Transmitral flow is also augmented by atrial contraction, so its absence in atrial fibrillation is often poorly tolerated.
Mitral Regurgitation
During mitral regurgitation, the left ventricle preferentially empties into the left atrium before the aortic valve opens. This is due to the low pressure system that exists between the left ventricle and left atrium. As a result, there is more complete left ventricular emptying. Initial measures of cardiac function reveal an increase in ejection fraction but with a reduced forward stroke volume. The left ventricle can also dilate to ensure adequate forward flow early on, but may eventually decompensate and produce the clinical picture of heart failure.
Mitral Valve Prolapse
Although specific pathological features have been established for the diagnosis, echocardiography is the most common and most appropriate initial test used to diagnose MVP (Douglas, Khandheria, Stainback, & Weissman, 2007; guideline available at content.onlinejacc.org/article.aspx?articleid=1138325&resultClick=1). There is a wide range of clinical findings, from a mid-systolic click and murmur due to prolapse of the posterior leaflet to severe mitral regurgitation. In the latter condition, the pathophysiology resembles non-MVP forms of mitral regurgitation. Hemodynamically, the prolapse is exacerbated whenever left ventricular volume is reduced and during hyperdynamic states. Patients therefore often become more symptomatic when intravascular volume is depleted, as seen during dehydration or when given excessive diuretics. Vasodilators may also compound the problem.
Aortic Stenosis
In aortic stenosis, obstruction to left ventricular outflow occurs gradually. As a compensatory mechanism, cardiac output is maintained by the development of left ventricular hypertrophy in order to create and sustain the increased pressure gradient across the aortic valve. Clinically significant aortic stenosis occurs when cardiac output cannot be augmented to meet systemic demands. In addition, pressure is transmitted back to the left atrium and beyond; pulmonary congestion and right ventricular failure can result.
Aortic Regurgitation
Analogous to mitral regurgitation, the proximal chamber (the left ventricle in this case) is exposed to an increase in blood volume. The difference, however, is that the entire left ventricular stroke volume is ejected into the high-pressure aorta rather than the low-pressure left atrium as seen in mitral regurgitation. As a consequence, the left ventricle must often undergo a combination of hypertrophy and dilatation to provide a normal effective forward stroke volume. A higher-than-normal ejection fraction is the expected finding.
EPIDEMIOLOGY
Mitral Stenosis
Mitral stenosis is usually a consequence of rheumatic heart disease and primarily affects women. The steady decline in the incidence of rheumatic fever in the United States and other developed countries is followed by a reduction in the incidence of mitral stenosis (Shulman, Stollerman, Beall, Dale, & Tanz, 2006). In developing nations, however, both rheumatic fever and mitral stenosis remain a common cause of valvular disease.
Although mitral valve involvement occurs in up to half of acute rheumatic fever cases (Marijon, Mirabel, Celermajer, & Jouven, 2012), patients rarely recall having had rheumatic carditis. So, while inquiring about a history of rheumatic fever is pertinent, a negative history is not helpful in excluding the etiology of mitral stenosis. In rheumatic heart disease, combined mitral stenosis and mitral regurgitation is the most common finding, followed by multivalve involvement including the mitral valve. Isolated mitral stenosis is seen in 40% of all patients with rheumatic heart disease (Bonow et al., 2008).
Mitral Regurgitation
Many congenital and acquired conditions affect the mitral valve. The mitral valve apparatus includes the annulus, mitral leaflets, chordate tendineae, and papillary muscles, and requires that they operate in a coordinated manner. Disturbances to any of these structures may cause mitral valve dysfunction and subsequent regurgitation.
The causes of mitral regurgitation depend on whether the onset is acute or chronic. Acute mitral regurgitation is usually the result of myocardial ischemia, infective endocarditis, or trauma. Chronic mitral regurgitation is most often due to MVP, but other causes include collagen vascular disease, infective endocarditis, rheumatic fever, cardiomyopathies, and congenital heart disease involving the mitral valve.
Mitral Valve Prolapse
MVP deserves special mention when discussing mitral regurgitation because of the frequency with which it is diagnosed in the general population. Although its prevalence had initially been reported as high as 15%, later reports document the prevalence as closer to 2.4%, which is still a significant proportion (Guy & Hill, 2012).
MVP is caused by myxomatous degeneration involving the valve, and is typically manifested as a genetic form of connective tissue disorder. It is frequently seen in association with other collagen diseases such as Marfan syndrome, osteogenesis imperfecta, and Ehlers–Danlos syndrome. While it is commonly seen in women in the second and third decades of life, MVP may also be found in older patients as well as men. It is the most common cause of mitral regurgitation among those requiring surgery. MVP has also been referred to as the systolic click-murmur syndrome, Barlow syndrome, billowing mitral cup syndrome, or floppy valve syndrome.
Aortic Stenosis
Aortic stenosis is usually due to degeneration and calcification of a congenitally bicuspid or normal trileaflet valve. Recent advances in understanding the pathogenesis of this condition suggest an active disease process that includes abnormal lipid accumulation, inflammation, and calcification. Some risk factors for the development of aortic stenosis as well as the pathological findings are similar to those associated with coronary atherosclerosis, such as hypertension, hypercholesterolemia, calcification related to renal disease, and even infection with Chlamydia pneumoniae (Chan, 2003; Freeman & Otto, 2005; Juvonen et al., 1997). Unfortunately, studies attempting to modify such risk factors have been inconsistent in demonstrating a slowing of the progression toward more severe aortic stenosis (Cowell et al., 2005; Moura et al., 2007; Rossebø et al., 2008).
The underlying valve substrate depends on the age at clinical presentation. For those older than 70 years, the most common cause is calcific aortic stenosis involving a tricuspid valve. Bicuspid aortic valves represent the predominant valve type in those who develop aortic stenosis younger than 70 years of age. It is the most common congenital heart valve defect and is more prevalent in men. Patients with bicuspid aortic valves are not only prone to develop aortic stenosis, but often have dilatation of the ascending aorta and are at risk of aortic dissection (Borger et al., 2004).
Aortic Regurgitation
Aortic regurgitation results from disease processes of the aortic leaflets or aortic root that prevent proper coaptation of the valves. Leaflet abnormalities that result in aortic regurgitation can be secondary to calcification of the aortic valve, which does not allow effective closure of the valve cusps. Aortic regurgitation is often seen in association with aortic stenosis, infective endocarditis, and rheumatic fever. Aortic root causes include degenerative aortic dilatation, Marfan syndrome, aortic dissection, collagen vascular disease, syphilis, and annuloaortic ectasia. The end result is dilation of the aortic annulus, which effectively pulls the valve leaflets away from each other and allows regurgitant flow in diastole.
HISTORY AND PHYSICAL EXAMINATION
Mitral Stenosis
There is a long latent period between the rheumatic fever episode and clinical symptoms, which typically begin in the fourth decade of life. Patients usually have minimal or no symptoms when the disease is mild. With progressive stenosis, the most common symptoms are dyspnea and fatigue, and may include orthopnea and paroxysmal nocturnal dyspnea. While these resemble the common heart failure complaints, the left ventricle is minimally affected because the pathological process occurs proximal to this chamber. Occasionally, the left ventricular ejection fraction may be reduced due to excessive afterload secondary to a reflexive increase in systemic vascular resistance (Gash, Carabello, Cepin, & Spann, 1983).
Signs of right heart failure may also be present when the increased left atrial pressure is transmitted across the pulmonary vasculature; these include hepatomegaly, ascites, and peripheral edema. Other manifestations of elevated right-sided filling pressures include hemoptysis from ruptured bronchial veins and hoarseness due to compression of the left recurrent laryngeal nerve from a distended left atrium (Ortner syndrome).
On cardiac examination, an irregularly irregular pulse indicating atrial fibrillation may be present. The S1 is characteristically loud because the mitral valve is held in the open position by the increased transmitral gradient until the force of ventricular systole closes the valve. The opening snap (OS) of the mitral valve may be heard, with the interval between A2 and OS inversely related to the severity of mitral stenosis. A loud P2, right ventricular lift, elevated neck veins, ascites, and edema are indicators of pulmonary hypertension. This is an ominous sign in the progression of the disease because the risk associated with mitral surgery increases.
The diastolic murmur of mitral stenosis varies with the respiratory cycle, softening during inspiration and augmenting during expiration. The strain phase of the Valsalva maneuver diminishes the murmur, whereas squatting increases it.
Mitral Regurgitation
The majority of patients with mitral regurgitation experience few symptoms. Over time, chronic mitral regurgitation can expose the left ventricle to a volume overloaded state resulting in compensatory chamber dilatation. When the left ventricle weakens and loses its ability to maintain an adequate cardiac output, symptoms of heart failure may develop. The major symptoms are similar to those of mitral stenosis, including fatigue and exertional dyspnea. Signs of right heart failure may also be present. Palpitations may be felt and indicate the presence of atrial fibrillation.
Cardiac examination reveals a hyperdynamic left ventricle, where a systolic thrust or thrill can sometimes be appreciated. The S1 is diminished. There is often wide splitting of the second heart sound. A holosystolic murmur heard on physical examination is often the finding that first alerts the examiner to the presence of mitral regurgitation. The murmur is loudest at the apex and usually radiates to the axilla. An S3 heard in mitral regurgitation, however, does not necessarily indicate the presence of heart failure, because rapid left ventricular filling due to a large residual volume of blood stored in the left atrium is the cause of the sound in this situation. The murmur of mitral regurgitation is intensified by isometric exercise and diminishes with sudden standing or with the Valsalva maneuver. The act of squatting increases left ventricular volume and results in a louder murmur.
Mitral Valve Prolapse
Most patients with MVP do not experience symptoms and remain asymptomatic throughout their lives. The symptoms that have been described are not all well explained by the underlying pathological process. Patients may note palpitations, dizziness, syncope, chest discomfort, or complaints similar to those of decompensated heart failure and mitral regurgitation. There is often a dissociation between the severity of the prolapse or regurgitation and the intensity of symptoms.
The classical findings of MVP on physical examination are a midsystolic click followed by a late crescendo systolic murmur. There are variations to this presentation, such as single or multiple clicks alone or an isolated murmur. In addition, different auscultatory findings may be heard in the same patient at different times. When the Valsalva maneuver is performed, left ventricular filling is reduced during the strain phase, causing the click and onset of the murmur to occur earlier during systole.
Aortic Stenosis
Most patients with aortic stenosis remain asymptomatic until the valve area approaches a critical value. Even at that stage not all patients have complaints, which is an important indicator of the need for mechanical intervention (Dal-Bianco, Khandheria, Mookadam, Gentile, & Sengupta, 2008). The classic symptoms of severe aortic stenosis are angina, syncope, and signs and symptoms of heart failure. Angina in aortic stenosis has characteristics similar to angina from coronary disease; it is exacerbated by exertion and relieved by rest. This is due to increased oxygen demands of hypertrophied myocardium and reduced blood flow secondary to myocardial compression of the coronary arteries. Coronary artery disease is present in 50% of cases and may cause angina due to intracoronary obstruction in addition to the noncoronary reasons stated earlier (Otto, 2006). Syncope is often exertional and is a result of reduction in cerebral blood flow. In the presence of a fixed cardiac output, blood is shunted away from the brain to the rest of the body due to systemic vasodilation, resulting in less blood flowing into the brain. Heart failure, usually heralded by dyspnea, may be seen in the presence of a preserved ejection fraction (diastolic dysfunction), reduced ejection fraction (systolic dysfunction), or both. Heart failure with preserved ejection fraction results in increased left ventricular end-diastolic pressure leading to pulmonary congestion. Heart failure with reduced ejection fraction may also result in increased left ventricular filling pressures and lead to reduced exercise tolerance and shortness of breath.
A systolic ejection murmur radiating to the neck is the most common sign of aortic stenosis. It is heard loudest in the second right intercostal space and is characteristically harsh and low pitched. The murmur may disappear over the sternum only to reappear at the apex, mimicking the findings of mitral regurgitation (Gallavardin phenomenon). In mild aortic stenosis, the murmur peaks early in systole. As the severity of stenosis increases, the murmur peaks progressively later in systole and may become softer as the cardiac output diminishes. The carotid upstrokes classically become diminished in amplitude and delayed in time (parvus et tardus). S2 may become paradoxically split because of the delay in left ventricular emptying, or the second heart sound may become single because the aortic closing component is lost.
Maneuvers that reduce left ventricular volume, such as Valsalva or standing, will soften the systolic murmur of aortic stenosis. Handgrip will also decrease the murmur, whereas squatting augments it.
Aortic Regurgitation
Chronic severe aortic regurgitation imposes a pressure and volume load on the left ventricle. Although the ventricle enlarges in response to this, most patients remain asymptomatic. It is usually after significant cardiomegaly and myocardial dysfunction have occurred that symptoms from diminished cardiac reserve surface. Exertional dyspnea, orthopnea, and paroxysmal nocturnal dyspnea then start to appear. Angina, particularly nocturnal angina, may appear even in the absence of coronary artery disease and seem to be caused by diastolic pressure falling to low levels.
The large total stroke volume in aortic regurgitation increases pulse pressure, producing a host of clinical signs. Although the diastolic blowing murmur heard along the left sternal border is the typical sign of aortic regurgitation, peripheral signs of a hyperdynamic circulation may be detected and often indicate severe disease. Table 13.1 is a partial list of these signs, along with their eponyms.
In addition to the murmur of aortic insufficiency, a diastolic rumble (Austin Flint murmur) may also be heard over the cardiac apex. Although its cause is unsettled, the Austin Flint murmur is probably produced as the aortic jet impinges on the mitral valve, causing it to vibrate. Simultaneously, diastolic filling of the left ventricle from the left atrium and aorta tends to close the mitral valve in diastole, producing a physiological mitral stenosis.
